The Centers for Disease Control and Prevention estimates that as many as 1.7 million people in the United States experience a traumatic brain injury (TBI) each year, over 15% of which are thought to be sports-related. Despite the relatively high prevalence of these injuries, however, it seems we are just beginning to appreciate the true extent of the effects they can have on the brain. Awareness of previously unrecognized consequences to TBI and repeated TBI--along with the realization that TBI may occur more frequently than previously believed in high-impact sports like American football--has sparked a great deal of interest in gaining a better understanding of the neurobiological consequences of these injuries.

Types of TBI

TBI can be considered acute, which refers to a recent injury and its short-term effects, or chronic, which describes the accumulated neurobiological effects of repeated TBI. The most common acute TBI is mild TBI, which is also known as a concussion. A concussion doesn't result in any overt pathology (e.g. bleeding, obvious structural damage) in the brain, but can cause a variety of symptoms including dizziness, nausea, headache, impairments in concentration and memory, and even loss of consciousness. The discernibility of symptoms can range from very apparent to subtle enough that they are difficult to detect without formal assessment. For some, these symptoms will disappear within minutes to hours after the injury. However, about 40-80% of people who experience a concussion will develop post-concussion syndrome, which involves prolonged symptoms that last for days or weeks. At least 10% may develop persistent post-concussive syndrome, which entails symptoms that persist for more than 3 months and can continue for longer than a year.

Of course acute TBI can also be much more severe than what is seen in a typical concussion, and can result in contusions (bruises) and/or lacerations of brain tissue as well as potential intracranial bleeding (i.e. bleeding within the skull). Acute TBI of this severity is known as catastrophic brain injury, and may result in death. The most common cause of death in these cases is subdural hematoma, which is a pooling of blood between the dura mater and brain. Such accumulation can increase intracranial pressure to dangerous levels, which can cause damage to (and death of) brain tissue.

The effects of repeated TBI, as may occur in someone who plays a contact sport like American football professionally, can lead to accumulative damage to the brain referred to as chronic traumatic encephalopathy (CTE). This syndrome has long been recognized as a hazard of a career in boxing, causing it to initially be referred to as "punch-drunk syndrome" before it was given the more formal appellation of dementia pugilistica in the 1930s. The disorder has some similarities to dementia, and is associated with cognitive decline, tremors and other movement problems, as well as difficulties with speech that make speech sound slurred (hence the reference to drunkenness in the original descriptor of the syndrome). The overt symptoms of CTE often do not appear until long after the repeated head trauma (e.g. after a boxer has already retired), frequently emerging in midlife, but about 1/3 of CTE cases get progressively worse over time.

Pathophysiology of TBIs

Damage to the brain in TBI can be classified as either focal or diffuse. Focal damage usually occurs after direct impact to a specific part of the head/brain that results in damage that is observable with the naked eye. Focal injuries thus tend to be more severe and involve damage like contusions, lacerations, and hemorrhages. Diffuse injuries, on the other hand, are present in both severe and more mild forms of TBI and are not generally visible without the use of advanced neuroimaging techniques. Diffuse injuries are created when brain tissue is stretched and torn due to the rapid acceleration and deceleration of the head that can be caused by sudden impacts. In this article, I will focus primarily on diffuse injuries as they are the type of injury whose effects can accumulate over time with repeated trauma--even if the injuries themselves are relatively mild in terms of symptoms produced. Thus, while focal injuries are recognized as cause for immediate concern, diffuse injuries can, for example, affect athletes over the course of a career without debilitating symptoms only to lead to premature cognitive decline once the career has ended.

Neurochemical effects

As the disruption of the integrity of axons due to DAI is occurring, there are also widespread changes in neurochemistry that develop, precipitated at least in part by the degeneration of axons. As axons deteriorate, the flow of ions across the neuronal membrane is dysregulated, leading to the excessive release of neurotransmitters like the excitatory neurotransmitter glutamate. The increased release of glutamate causes extensive neuronal excitation; the brain responds by using large amounts of energy to attempt (unsucessfully) to contain this exaggerated neural activity. However, there is not enough glucose to fully meet this energy need, and the brain resorts to a method to generate short-term energy that leads to the accumulation of the compound lactate. Lactate build-up can cause additional neuronal dysfunction, and might make neurons more susceptible to damage should another injury occur.

When glutamate binds to its receptors on neurons, it causes calcium ions to enter the cell. Due to the high levels of glutamate present after TBI, calcium influx into neurons becomes excessive. This can lead to the accretion of calcium within mitochondria, and the subsequent disruption of mitochondrial energy production. In severe cases, intracellular calcium build-up can prompt neurons to initiate apoptotic processes (i.e. neurons commit "cell suicide" due to the negative metabolic consequences of intracellular calcium accumulation).

Dangerous impact

Thus, when a TBI occurs there are substantial effects on the brain, some of which resemble the same types of neurobiological changes we see in our most devastating neurodegenerative diseases. A better understanding of TBI and its consequences has made the potential effects of repeated head injuries an important topic of sports-related discussions, as it is becoming recognized that popular sports like American football (which are often played by teenagers and adolescents) may pose a risk to the health of their participants. Studies of professional football players, for example, have provided ominous results; in one large study that included the brains of 91 professional football players donated for post-mortem analysis, 87 had evidence of CTE.

Concerns also abound for other sports that involve frequent head impacts. Boxing and mixed martial arts are obvious culprits. The available data on the risks inherent to boxing are extensive; the literature on mixed martial arts is more limited, likely due to its relatively recent increase in popularity. However, one can assume that (at least on the professional level) there is some overlap in the degree of risk involved in all combat sports due to the frequent head impacts involved, and the results of studies that have focused on combat sports have generally been concerning. For example, one study found that 87% of former boxers examined displayed evidence of brain dysfunction as indicated by a CAT scan, electroencephalogram, or neuropsychological testing. Another study of neuroimaging results from 100 boxers and mixed martial artists found 76% of them had brain abnormalities consistent with TBI, and the severity of these abnormalities was correlated with the number of fights they had in their career. This should come as no surprise when we consider the results of one study of the force of impact of a punch from a professional heavyweight boxer (former champion Frank Bruno): it was found to be equivalent to the force generated by a 13-pound wooden mallet swung at a speed of 20 miles per hour.

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